Cellular Mechanisms of Photoreceptor Disk Morphogenesis

项目摘要 光感受器纤毛是所有初级纤毛中最精细的。它的质膜广泛地 被放大以形成含有非常高浓度的视觉感受器的盘膜的堆叠， 视蛋白这一堆圆盘形成了感光器外节，其组织对于视觉至关重要 灵敏度和空间分辨率。拟议研究的总体目标是了解细胞 在磁盘膜的形态发生机制。 该研究计划建立在分子工具的应用基础上，使用先进的显微镜， 包括EM断层扫描和活细胞超分辨率显微镜，用于高分辨率，3-D分析。的 这项研究的长期目标是从分子水平上了解感光盘 形态发生，包括将必需蛋白质递送到膜生长位点的机制。 具体目标将解决视蛋白的睫状定位的未知方面，以及磁盘的作用 形态发生蛋白在启动板层生长中的作用， 带有非特化纤毛的细胞培养物。我们的研究结果将提供一个关键领域的理解， 感光细胞生物学它们也将是我们理解视网膜病变发病机制的基础。 由于盘膜形态发生的紊乱而引起的疾病。

Project Summary The photoreceptor cilium is the most elaborate of all primary cilia. Its plasma membrane is extensively amplified to form a stack of disk membranes that contain a very high concentration of the visual receptor, opsin. This stack of disks forms the photoreceptor outer segment, and its organization is central to visual sensitivity and spatial resolution. The overall goal of the proposed research is to understand the cellular mechanisms involved in the morphogenesis of the disk membranes. The research plan is built on the application of molecular tools, with the use of advanced microscopy, including EM tomography and live-cell super-resolution microscopy, for high resolution, 3-D analysis. The long-term goal of the proposed research is to provide a molecular understanding of photoreceptor disk morphogenesis, including the mechanisms for delivering essential proteins to the site of membrane growth. The Specific Aims will address unknown aspects of the ciliary localization of opsin, and the roles of disk morphogenetic proteins in initiating lamellar growth, using both mouse rod photoreceptors in vivo and cultures of cells bearing unspecialized cilia. Our findings will provide understanding of a key area of photoreceptor cell biology. They will also be fundamental to our understanding of the pathogenesis of retinal disease that ensues from perturbations of disk membrane morphogenesis.